Aromatic substituted amidines

ABSTRACT

1. A COMPOUNDD OF THE FORMULA   AR-(CH2)N-C(-N=Z)=N-R   WHEREIN AR US UNSUBSTITUTED PYRIDYL OR PHENYL SUBSTITUTED BY FROM ONE TO THREE SUBSTITUENTS SELECTED FROM THE GROUP CONSISTING OF HALOGEN, TRIFLUOROMETHYL, TRIFLUOROMETHOXY, NITRO, LOWER-ALKOXY, LOWER-ALKYKLTHIO, LOWER-ALKYLSULFOXY, LOWER-ALKYLSULFONYL, AMINO, LOWER - AKANOYLAMINO, BIS(METHYLSULFONYL)AMINO, SULFAMYL, LOWER-ALKYLLSULFAMYL, AND DI-LOWER-ALKYLSULFAMYL: N IS 0: N=Z IS UNSUBSTITUTED POLYMETHYLENIMINO HAVING FROM 7 TO 9 RING MEMBERS; AND R IS LOWER-ALKYL, LOWER -ALKENYL, CYCLOALKYL OF 3-6 RING MEMBERS, CYCLOALKYL-LOWER-ALKYL WHEREIN CYCLOALKYL HAS 3-6 RING MEMBERS, PHENYL-LOWER - ALKYL, HYDROXYL-LOWERALKYL, OR LOWER-ALKANOYLOXY-LOWER-ALKYL.

United States Patent U.S. Cl. 260-439 B 44 Claims ABSTRACT OF THE DISCLOSURE Substituted amidines of the formula Ar(CH C(N=Z)=NR where Ar is unsubstituted pyridyl or substituted phenyl, n is 0 or an integer from 1 to 3, N=Z is 7-9 ring membered polymethylenimino and R is lower-alkyl, loweraikenyl or substituted lower-alkyl, having diuretic and antiinfiammatory activity, are prepared by interacting an amide of the formula Ar(CH CONHR with phosphorus pentachioride, and interacting the resulting imidyl chloride, Ar(CH C(Cl)=NR with a secondary-amine, HN:

This application is a continuation-in-part of my prior copending application, Ser. No. 796,187, filed Feb. 3, 1969, now US. Pat. 3,697,505.

This invention relates to aromatic substituted amidines, and more particularly is concerned with amidines completely substituted on the nitrogen atoms, and substituted on the carbon atom by monocarbocyclic aryl or pyridyl groups, and with methods for their preparation.

The compounds of the invention are represented by the following structural formula wherein Ar is unsubstituted pyridyl or phenyl substituted by from one to three substituents selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, nitro, lower alkoxy, lower-alkylthio, lower-alkylsulfoxy, lower-alkylsulfonyl, amino, lower-alkanoylamino, bis (methylsulfonyDamino, sulfamyl, lower-alkylsulfamyl and di-lower-alkylsulfamyl; n is 0 or an integer from 1 to 3; N=Z is a polymethylenimino having from 7 to 9 ring members; and R is lower-alkyl, lower-alkenyl, cycloalkyl of 3-6 ring members, cycloalkyl-lower-alkyl wherein cycloalkyl has 3-6 ring members, phenyl-lower-alkyl, hydroxy-lower-alkyl or lower-alkanoyloxy-lower-alkyl.

In the foregoing definitions the terms lower-alkyl, low er-alkoxy, lower-alkenyl and lower-alkanoyloxy refer to such groups having up to six carbon atoms and which can have straight or branched chains.

In the above formula I, N=Z stands for polymethylenimino having from 7 to 9 ring members and a total of from six to about twelve carbon atoms, for example, hexamethylenimino, heptamethylenimino, octamethylenimino and lower-alkylated derivatives thereof.

The compounds of formula I are prepared by the following reaction scheme:

3,850,909 Patented Nov. 26, 1974 An acid chloride of formula II is treated with a primaryamine, H NR, to produce the amide of formula III. The amide III is then treated in an inert solvent with phosphorus pentachloride to produce the imidyl chloride of formula IV. The reaction takes place at a temperature between about 50 and C., conveniently at the reflux temperature of the inert solvent. The phosphorus pentachloride can be replaced by thionyl chloride if desired. The final step comprises treating the imidyl chloride IV with a secondary-amine, HN=Z, in an inert solvent. The reaction takes place at a temperature between about 20 and 150 C.

The compounds of formula I wherein n is 1-3 can be prepared by an alternative route as follows:

An aryl lower-alkyl ketone heated with a secondary amine, HN=Z, and sulfur gives a thioamide of formula V. The latter is then interacted with a primary-amine, H NR, in the presence of mercuric chloride to give a compound of formula I wherein n is 1-3.

The compounds of the invention of formula I are basic in nature and readily form acid-addition or quaternary ammonium salts. Said acid-addition and quaternary ammonium salts are within the purview of the invention and are the full equivalents of the free bases claimed herein.

It is thus be appreciated that formula I not only represents the structural configuration of the bases of formula I but is also representative of the respective structural entity which is common to all of the respective compounds of formula I whether in the form of the free bases or in the form of the acid-addition or quaternary ammonium salts of the bases. By virtue of this common structural entity, the bases and their salts have inherent bio logical activity of a type to be more fully described hereinbelow. When used for pharmaceutical purposes one can employ the free bases themselves or the acid-addition or quaternary ammonium salts formed from pharmaceutically-acceptable acids or esters, that is, acids or esters whose anions are innocuous to the animal organism in effective doses of the salts so that beneficial properties inherent in the common structural entity represented by the free bases are not vitiated by side-effects ascribable to the anions.

In utilizing the pharmacodynamic activity of the salts of the invention, pharmaceutically-acceptable salts are preferred. Although water-insolubility, high toxicity, or lack of crystalline character may make some particular salt species unsuitable or less desirable for use as such in a given pharmaceutical application, the water-insoluble or toxic salts can be converted to any desired pharmaceutically-acceptable salt by double decomposition reactions involving the anion, for example, by ion-exchanged procedures. Moreover, apart from their usefulness in pharmaceutical applications, the salts are useful as characterizing or identifying derivatives of the free bases or in isolation or purification procedures.

It will be appreciated from the foregoing that all of the acid-addition and quaternary ammonium salts of the new bases of the invention are useful and valuable compounds, regardless of considerations of solubility, toxicity,

physical form, and the like, and are accordingly within the purview of the instant invention.

The novel feature of the compounds of the invention, then, resides in the concept of the bases and cationic forms of the basic compounds of formula I and not in any particular acid moiety or acid anion associated with the salt forms of the compounds; rather, the acid moieties or anions which can be associated in the salt forms are in themselves neither novel nor critical and therefore can be any acid anion or acid-like substance capable of salt formation with bases. In fact, in aqueous solutions, the base form or water-soluble acid-addition salt form of the compounds of the invention both possess a common protonated cation or ammonium ion.

Thus the acid-addition salts discussed above and claimed herein are prepared from any organic acid, inorganic acid (including organic acids having an inorganic group therein), or organo-metallic acid as exemplified by organic monoand polycarboxylic acids. Illustrative acid-addition salts are those derived from such diverse acids as formic acid, acetic acid, isobutyric acid, alpha-mercaptopropionic acid, malic acid, fumaric acid, succinic acid, succinamic acid, tartaric acid, citric acid, lactic acid, benzoic acid, 4-methoxybenzoic acid, phthalic acid, anthranilic acid, l-naphthalenecarboxylic acid, cinnamic acid, cyclohexanecarboxylic acid, cyclohexanesulfamic acid, mandelic acid, tropic acid, crotonic acid, acetylene dicarboxylic acid, sorbic acid, 2-furancarboxylic acid, cholic acid, pyrenecarboxylic acid, Z-pyridinecarboxylic acid, 3-indoleacetic acid, quinic acid, sulfamic acid, methanesulfonic acid, isethionic acid, benzenesulfonic acid, p-toluenesulfonic acid, benzenesulfinic acid, butylarsonic acid, diethylphosphinic acid, p-aminophenyl arsinic acid, phenylstibnic acid, phenylphosphinous acid, methylphosphinic acid, phenylphosphinic acid, hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydriodic acid, perchloric acid, nitric acid, sulfuric acid, phosphoric acid, hydrocyanic acid, phosphotungstic acid, molybdic acid, phosphomolybdic acid, pyrophosphoric acid, arsenic acid, picric acid, picrolonic acid, barbituric acid, boron trifluoride, and the like.

The acid-addition salts are prepared either by dissolving the free base in an aqueous solution containing the appropriate acid and isolating the salt by evaporating the solution, or by reacting the free base and acid in an organic solvent, in which case the salt separates directly or can be obtained by concentration of the solution.

The quaternary ammonium salts of the basic compounds of formula I are obtained by the addition of esters of strong acids to the free base form of the compounds, said esters having a molecular weight less than about 300. A preferred class of esters comprises alkyl, alkenyl, and monocarbocyclic aryl-lower-alkyl esters of strong inorganic acids or organic sulfonic acids, including such compounds as methyl chloride, methyl bromide, methyl iodide, ethyl bromide, propyl chloride, allyl chloride, allyl bromide, methyl sulfate, methyl benzenesulfonate, methyl p-toluenesulfonate, benzyl chloride, benzyl bromide, and substituted benzyl halides, for example pchlorobenzyl chloride, 3,4-dichlorobenzyl chloride, 2,3,4, 5,6-pentachlorobenzyl chloride, 4-nitrobenzyl chloride, 4- methoxybenzyl chloride, and the like.

The quaternary ammonium salts are prepared by mixing the free base and ester of a strong acid in an inert solvent. Heating may be used to facilitate the reaction, although salt formation usually takes place readily at room temperature. The quaternary ammonium salt separates directly or can be obtained by concentration of the solution.

As in the case of the acid-addition salts, water-insolubility, high toxicity, or lack of crystalline character may make some quaternary ammonium salt species unsuitable or less desirable for use as such in a given application, the water-insoluble or toxic salts can be converted to the corresponding pharmaceutiCally-acceptable salts by double decomposition reactions involving the anion, for example, by ion-exchange procedures. Alternatively, if the anion of the original quaternary salt forms a water-insoluble silver salt, the quaternary salt will react with silver oxide in aqueous medium to form the corresponding quaternary ammonium hydroxide, the original anion being removed as a precipitate. The quaternary ammonium hydroxide solution can then be neutralized with any desired acid, weak or strong, to produce a new quaternary ammonium salt in which the anion is different from that of the original salt. In this way quaternary ammonium salts in which the anion is derived from a weak acid are formed.

Pharmacological evaluation of the compounds of formula I has shown that they possess diuretic, natriuretic, and anti-inflammatory activity upon oral administration. These activities were demonstrated in dogs and rats by standard test procedures.

The diuretic and natriuretic activities in dogs were determined by the method of McKeon, Ach. Int. Pharmacodyn. 151, 22542 (1964), whereby the effect of oral administration of the test compounds upon the volume and the sodium, potassium and chloride ion content of the urine was determined.

The diuretic and natriuretic activity in rats was determined according to the procedure of Williamson et al., J. Pharm. & Exptl. Therap. 126, 82 (1959). The compound to be tested was administered orally. A control group of animals was treated with 8 micromoles/kg. of the standard drug, hydrochlorothiazide. The dose of the test compound Which produced a response half that of the reference drug, hydrochlorothiazide, was then reported as the approximate minimal effective dose.

The anti-inflammatory activity was measured by the inhibition of carrageenin-induced local foot edema in rats according to the method of Winter et al., Proc. Soc. Exptl. Biol. & Med. 111, 544 (1962), and by the inhibi- ,tion of pleurisy in rats acording to the method of Wilhelmi [Non-steroidal Anti-Inflammatory Drugs, Proceedings of an International Symposium, Milan, 1964, Excerpta Medica Foundation, Amsterdam].

In the carrageenin-induced edema inhibition tests, one hour following medication, 0.05 ml. of 1% aqueous suspension of carrageenin was injected into the plantar tissue of their right hind foot and 0.05 ml. of saline similarly into the left foot. Three hours after injection, the rats were sacrificed and the hind feet cut off at the tibio-calcaeno-talar joint for subsequent weighing. The observed differences between the average edema weight of the control and medicated rats were expressed as percent inhibition of edema.

In the pleurisy inhibition tests, the degree of inhibition of pleural exudate formation induced by silver nitrate as an irritant in the medicated rats as compared with control rats was a measure of the anti-inflammatory activity.

The actual determination of the numerical biological data definitive for a particular compound is readily ob tained by standard test procedures by technicians trained in pharmacological test procedures, without the need for any extensive experimentation. The compounds are effective in amounts of 5-50 micromoles per kilogram depending upon the compound used and the manner of administration. They are prepared for use by conventional pharmaceutical formulation procedures, that is, in capsule or tablet form with conventional excipients (for example, calcium carbonate, starch, lactose, talc, magnesium stearate, gum acacia, and the like) for oral administration; or as an aqueous or oil suspension in a pharmaceutically acceptable vehicle (aqueous alcohol, glycol, oil solution, or oil-water emulsion) for parenteral administration.

The structures of the compounds of the invention were established by the modes of synthesis, by elementary analysis, and by infrared, ultraviolet and nuclear magnetic resonance spectral determinations.

The following examples will further illustrate the inven; tion without the latter being limited thereby.

5. A. BENZAMIDE DERIVATIVES AND ANALOGS Example A] N-Allyl 4 clilorobenzamide [111; Ar is 4-ClC H n is 0,

R is CH=CH A solution of 28.5 g. of allylamine in 250 ml. of chloroform was cooled in an ice bath. p-Chlorobenzoyl chloride (44 g.) was added dropwise with stirring. The reaction "mixture was allowed to warm to room temperature and then stirred for three hours. The chloroform solution was washed with water and dilute hydrochloric acid, and dried over anhydrous calcium sulfate. The chloroform solution was concentrated in vacuo to remove the solvent, and the residue was crystallized from a cyclohexane n pentane mixture to give 37.94 g. of N-allyl 4 chlorobenzamide, m.p. 70-72 C.

Example A2 N-Cyclopropylmethyl 4 clilorobenzamicle [111, Ar is 4- ClC H n is O, R is CH CH(CH A mixture of 14.86 g. of cyclopropylmethylamine, 16.6 g. of pyridine and 200 ml. of chloroform was cooled to l5 C. p-Chlorobenzoyl chloride (36.7 g.) was added dropwise, and the reaction mixture was allowed to warm to room temperature and stirred for three hours. The solution was washed successively with water, dilute hydrochloric acid, dilute sodium bicarbonate and water, dried over anhydrous calcium sulfate and concentrated in vacuo. The residue was crystallized from cyclohexane to give 32.5 g. of N-cyclopropylmethyl-4-chlorobenzamide, colorless blade clusters, m.p. 116118 C.

Example A3 N-EIl1yl-4-elzl0r0benzamide [111; Ar is 4-ClC 1-I n is 0, R

is CH CH A solution of 17.7 g. of ethylamine in water was cooled to -5 C., and 17.5 g. of p-chlorobenzoyl chloride was added dropwise with stirring. The precipitate which formed was collected and dried to give N-ethyl-4-chlorooenzamide which was used directly to form the compound of Example B3 below.

Example A4 N (2 Hydroxyetlzyl) 4 chlorobenzamide [111; Ar is 4-C1C H n is 0, R is CH CH OH].

A mixture of 42.7 g. of methyl p-chlorobenzoate and 61.1 g. of ethanolamine was heated at reflux for three hours. The reaction mixture was poured into water, and the solid product collected by filtration and recrystallized from aqueous ethanol to give 30.5 g. of N-(Z-hydroxyethyl)-4-chlorobenzamide, m.p. 1081l3 C.

The following compounds were prepared by the methods of Examples Al, A2 or A3, using the appropriate acid chloride, Ar(CH- COCl, and amine, H NR:

Example A5: N-(n-Propyl)-4-clzl0r0ben2amide [111; Ar is 4-ClC H n is 0, R is CH CH CH (method A1), m.p. 96-98" C. (prisms from ether-pentane).

Example A6: N-Allyl 4 -flur0benzamicle [111; Ar is 4- FC H a is 0, R is CH CH=CH (method A1), m.p. 6769 C.

Example A7: N-Allyl-4-trifluorometlzylbenzamide [111; Ar is 4-F CC H n is O, R is CH CH=CH (method Al), pale yellow dendrite needles.

Example A8: N-Benzyl-4-chlorobenzamide [111; Ar is 4- ClC H n is 0, R is CH C H (method Al), m.p. l64 166 C. (fluffy needles).

Example A9: N-Cyclolzexylmetlzyl 4 chlorobenzamide [111; Ar is 4-ClC H n is 0, R is CH OH(CH (method A2), m.p. 117-119 C. (needles from cyclohexane).

Example A10: N-(Z-Baienyl)-4-chl0robenzamide [111; Ar is 4-ClC H n is 0, R is CH CH=CHCH (method A2), m.p. l10-1l2 C. (fragmented blades and needles from cyclohexane).

Example All: N-(n-Batyl)-4-chl0r0benzamide [111; Ar is 4-ClC H a is 0, R is CH CH CH CH (method A1), m.p. 80-82 C. (needles from cyclohexane).

Example A12: N-lsobutyl-4-chlorobenzamide [111; Ar is 4-ClC H n is O, R is CH CH(CH (method Al), m.p. 9395 C. (needles and platelets from cyclohexane).

Example A13: N-(2-Pl1enylethyl) 4 clzlorobenzamirle [111; Ar is 4*ClC H n is 0. R is CH CH C H (method Al), m.p. l34136 C. (needles from cyclohexane).

Example A14: N-Cycl0pr0pylmethyl 4 fluorabenzamide [111; Ar is 4-FC H n is 0, R is CH CH(CH (method A2), m.p. 87-97 C. (needles from cyclohexane).

Example A15: NA llylbenzamia'e [111; Ar is C H n is 0,

R is CH CH=CH (method Al), yellow oil.

Example A16: N-Allyl-4-brom0benzamide [111; Ar is 4- BrC H n is 0, R is CH CH==CH (method Al), m.p. 9294 C.

Example A17: N-(Z-Methylbutyl) 4 clzlarobenzamide [111; Ar is 4-ClC H n is 0, R is CH CH(CH CI-I CH (method Al), m.p. 54-64 C.

Example A18: N-(n-Propyl) benzamide [111; Ar is C H n is 0, R is CH CH CH (method A1), m.p. 82-84 C.

Example A19: N-(n-Propyl)-4-i0d0beazamide [111; Ar is 4-1C H n is 0, R is CH CH CH (method Al), m.p. l21l23 C.

Example A20: N-Cycl0pr0pylmetlzyl 4 iodobenzamiale [111; Ar is 4-1C H n is 0, R is CH CH(CH 1 (method A2). needles from ethyl acetate.

Example A21: N-Metlzyl-4-chl0r0benzamiale [111; Ar is 4- ClC H n is 0, R is CH (method A3), m.p. 153-155" C Example A22: N-(n-Propyl)-2,6-d cl1lorobenzamide [111; Ar is 2,6-C] C H n is 0, R is CH CH CH (method Al), m.p. 13ll33 C. (plates from ether).

Example A23: N-Is0pr0pyl-4-clzlorobenzamiae [111; Ar is 4-ClC H n is O, R is CH(CH (method Al), m.p. l42-l44 C. (needles from ethyl acetate).

Example A24: N-Cycl0pr0pyl-4-cl1lorobenzamide [111; Ar is 4-C1C H n is 0, R is CH(CH (method A2), m.p. l32133 C. (needles from ethyl acetate-cyclohexane).

Example A25: N-Isopropylnicotinamide [111; Ar is 3- pyridyl, n is 0, R is CH(CH (method Al), m.p. 9293 C. (from hexane).

Example A26: N-(n-Propyl)-4-nitr0benzamide [111; Ar is 4-O NC H n is O, R is CH CH CH m.p. 102-103.5 C. (from benezene-pentane).

Example A27: N-(n-Pr0pyl)-4-meth0xybenzamirle [111;

Ar 1S 4-CH3OCGH4, n is 0, R is cHgcHgcHg], 62-64 C. (from benezene-pentane).

Example A28: N-Isopropyl-2-chl0r0benzamide [111; Ar is 2-ClC H n is 0, R is CH(CH (method Al), m.p. 138-140 C.

Example A29: N-(n-Propyl)-D-metl1ylbenzamide [111; Ar

is 4-CH C H n is 0, R is CH C1-1 CH (method Al), m.p. 6667 C.

Example A30: N-Is0pr0pyl-3-clzl0r0ben2amide [111; Ar is 3-C1C H n is O, R is CH(CH (method Al), m.p. 8789 C.

Example A31: N-(n-Propyl)-3,4-dichl0robenzamide [111; Ar is 3, 4-Cl C H n is 0, R is CH C1-1 CH (method Al), m.p. 62 C.

Example A32: N-Isopropyl-3,4-a'ichlor0benzamia'e [111; Ar is 3,4-Cl C -H n is O, R is CH(CH (method Al), m.p. 123125 C.

Example A33: N-(n-Propyl) -3-meth0xy-4-chl0r0benzamia'e [111; Ar is 3-CH O-4-ClC H n is O, R is CH CH CH (method Al), colorless crystals.

Example A34: N-(n-Propyl)-3,5-diclzl0r0benzamide [111; Ar is 3,5-Cl C 1-I n is 0, R is CH CH CH (method A1), m.p. 203205 C.

Example A35: N-Isopropyl-2,4-dichlr0benzamide [III; Ar is 2, 4-Cl C H n is 0, R is CH(CH (method Al), m.p.121-130" C.

Example A36: N-(n-Propyl) -2,3-dichlor0benzamide [111; Ar is 2,4-Cl C H n is 0, R is CH CH CH (method A1), m.p. 9194 C.

Example A37: N-lsopropyl-4-trifluoromezhoxybenzamide [III; Ar is 4-F COC H n is 0, R is CH(CH (method Al), m.p. IOU-101 C.

Example A38: N-Is0pr0pyl-3,5-dichlorobenzamide [III; Ar is 3,5-Cl C H n is 0, R is CH(CH (method Al), m.p. 158160 C. (needles from chloroform).

Example A39: N-( 3 -H ydroxyproyl )-4-chlorobenzamide [III; Ar is 4-ClC H n is 0, R is CH CH CH OH] (Method A4), m.p. 105107 C. (colorless prisms from ethyl acetate).

Example A40: N-Isopropyl-2,5-dichl0rohenzamide [111;

Ar is 2,5-Cl C H n is 0, R is CH(CH (method Al), m.p. 131135 C.

Example A41: N-lsopropyl-3-nitro-4-ehlorobenzamia'e [111; Ar is 3-O N-4-ClC H n is 0, R is CH (CH (method Al), m.p. 1101 15 C.

Example A42: N-(n-Propyl-)-3-nitrobenzamide [111; Ar is 3O NC H n is 0, R is CH CI-I CH (method Al), m.p. 72-74 C.

According to the above procedures, 3,4,5-trimethoxybenzoyl chloride, p-methylthiobenzoyl chloride, p-methylsulfoxybenzoyl chloride, p-methylsulfonylbenzoyl chloride, phenylacetyl chloride, 4-chlorophenylacetyl chloride, [3- phenylpropionyl chloride, 'y-phenylbutyryl chloride, 2-pyr idylcarboxylic acid chloride, isonicothinoyl chloride or 3-pyridy1acety1 chloride can be interacted with isopropylamine to give, respectively, N-isopropyl-3,4,5-trimethoxy benzamide [111; Ar is (CH 0) C H n is 0, R is CH(CH N-isopropyl-4-methylthiobenzamide [III; Ar is 4-CH SC H n is O, R is CH(CH N-isopropyl-4- methylsulfoxybenzamide [III; Ar is 4-CH SOC H n is 0, R is CH(CH N-isopropyl-4-methylsulfonylbenzamide Al is 4-CH3SO2C6H4, n is 0, R is N-iSO- propylphenylacetamide [III; Ar is C H n is 1, R is CH(CH N isopropyl-4-chlorophenylacetamide [III; Ar is 4-ClC H n is 1, R is CH(CH N-isopropyl-flphenylpropionamide [III; Ar is C H n is 2, R is CH(CH N-isopropyl-v-phenylbutyramide [IIIg Ar is C H n is 3, R is CH(CH N-isopropyl-Z-pyridinecarboxamide [III; Ar is Z-pyridyl, n is 0, R is CH(CH N-isopropylisonicotinamide [III; Ar is 4-pyridyl, n is 0, R is CH(CH or N-isopropyl-3-pyridylacetamide [III; Ar is pyridyl, n is 1, R is CH(CH Example A43 1-(p-Chlor0pherzylthioacetyl) hexamethylenimi/re [Vg Ar is 4-ClC H n is 1, N=Z is N(CH A mixture of 49.4 g. of p-chloroacetophenone, 35 g. of hexamethylenimine, 15.35 g. of sulfur and 75 m1. of dimethylformamide was heated on a steam bath for about twenty hours. The reaction mixture was concentrated to remove the solvent and then shaken with water and ether. The ether layer was separated, dried over anhydrous calcium sulfate and concentrated, and the residue crystallized to give 18.32 g. of 1-(p-chlorophenylthioacetyl)hexamethylenimine, yellow needles, m.p. 8385 C. when recrystallized from cyclohexane.

By replacing the p-chloroacetophenone in the foregoing preparation by a molar equivalent amount of p-chlorobutyrophenone there can be obtained 1-[7- p-chlorophenyl)thiobutyryl]hexamethylenimine [[V; Ar is [4- ClC H n is 3, N=Z is N(CH 8 B. BENZIMIDYL CHLORIDE DERIVATIVES AND ANALOGS Example B1 N-Allyl-4-chlorobenzimidyl Chloride [IV; Ar is 4-ClC H n is 0, R is CH CH CH Phosphorus pentachloride (47.2 g.) and 250 ml. of benzene were stirred at reflux until the phosphorus pentachloride had dissolved. N-Allyl-4-chlorobenzamide (Example A1) (44.3 g.) was added in portions, and the reaction mixture was stirred at reflux until evolution of hydrogen chloride ceased (about four hours). The mixture was concentrated in vacuo to remove the solvent, and the residue was distilled to give 38.68 g. of N-allyl-4-chlorobenzimidyl chloride, b.p. 7282 C. (0.04 mm.), n =1.5727.

According to the foregoing procedure the following compounds were prepared from the compounds of the respective examples under section A.

Example B2: N-Cyclopropylmethyll-chlorobenzimidyl Chloride [IV; Ar is 4-ClC H n is 0, R is CH CH(CH b.p. 8l89 C. (0.03) mm.), n =1.570

Example B3: N-Ethyl-4-chlor0benzimidyl Chloride [IV;

Ar is 4-ClC H n is 0, R is CH CH b.p. -57 C. (0.03 mm.), n :1.5638.

Example B4: N-(Z-Chloroethyl-4-ehlorobenzimidyl Chloride [IV; Ar is 4-ClC H n is 0, R is CHgCHgCl], b.p. 1S1152 C. (5 mm.), n =1.5822.

Example B5: N-(n-Propyl)-4-chlorobenzimidyl Chloride [IV; Ar is 4-ClC H n is 0, R is CH CH CH b.p. 74 C. (0.015 mm.), n =1.5556.

Example B6: N-Allyl-4-fluorobenzimidyl Chloride [IV;

Ar is 4-FC H n is 0, R is CH CH=CH b.p. 4457 C. (0.03 mm.), n 25=1.5385.

Example B7: N-Allyl-4-triflu0romethylbenzimidyl Chloride [IV; Ar is 4-F CC H n is 0, R is CH CH=CH b.p. 44-48 C. (0.12 mm.).

Example B8: N-Benzyl-4-chlorobenzimidyl Chloride [IV; Ar is 4-CIC H n is 0, R is CH C H b.p. 117142 C. (0.07 mm.).

Example B9: N Cyclohexylmethyl 4 chlorobenzimidyl Chloride [IV; Ar is 4-ClC H n is 0, R is b.p. 126-132 C. (0.01 mm.), n =1.5628.

Example B10: N-(Z-Butenyl)-4-chlorobenzimidyl Chloride [IV; Ar is 4-ClC H n is 0, R is CH CH=CHCH b.p. -108 C. (0.35 mm.).

Example B11: N-Batyl-4-chlor0benzimidyl Chloride [IV;

AI' is 4-CICGH4, n is 0, R is CH CH CH CH 61-74 C. (0.1 mm.), n =1.5487.

Example B12: N-Isobutyl -4 -chlorobenzimidyl Chloride [IV; Ar is 4-ClC H n is 0, R is CH CH(CH b.p. 7078 C. (0.05 mm.), n =1.5455.

Example B13: N- (2 Phenylethyl) 4 chlorobenzimidyl Chloride [IV; Ar is 4-ClC H n is 0, R is z z s si b.p. 112-119 C. (0.04 mm.). Example B14: N-Cyel0propylmethyl-4flu0r0benzimidyl Chloride [IV; Ar is 4-FC H n is 0, R is b.p. 6575 C. (0.03 mm.), n =1.5385.

Example B15: N-Allylbenzimidyl Chloride [IV; Ar is C H n is 0, R is CH CH=CH b.p. 102105 C. (5 mm.), n =1.5575.

Example B16: N-Allyl-4-bromobenzimidyl Chloride [IV;

Ar is 4-BrC H n is 0, R is CH CH=CH b.p. 97- 104 C. (0.35 mm.), rn =1.5945.

Example B17: N-(2 Methylbutyl) 4 chlorobenzimidyl Chloride [IV; Ar is 4-ClC H n is 0, R is CH CH (CH CH CH b.p. 98108 C. (0.08 mm.), n =1.5430.

Example C22: 1-(NJsopropylnicotinimidoyl)hexamethylenimine [1; Ar is 3-pyridyl, n is 0, R is CH(CH N=Z is N(CH (from compound of Example B and hexamethylenimine), b.p. 85-87 C. (0.15 mm.), colorless waxy spherulites.

Example C23: J-[N-(n-Propyl)-4-nitr-obenzimidoyl]hexamethylenimine [1; Ar is 4-O NC H n is 0, R is CH CH CH N=Z is N(CH (from compound of Example B26 and hexamethylenimine), hydrochloride salt, m.p. 189-19l C., pale yellow prisms from acetone.

Example C24: I-[N-(n-Propyl)-4-methoxybenzimidayl] hexamethylenimine [1; Ar is 4-CH OC H n is 0, R is CH CH CH N=Z is N(CH (from compound of Example B27 and hexamethylenimine), hydrochloride salt, m.p. 158-159 C., colorless microprisms from ethyl acetate.

Example C25: 1-(N-Isopropyl-2-chlorobenzimidoyl)hexametlzylenimine [1; Ar is 2-ClC -H n is 0, R is CH(CH N=Z is N(CH (from compound of Example B28 and hexamethylenimine), b.p. 104-105 C. (0.050 mm.), n =1.5422.

Example C26: 1-(N-lsopropyl-3-chl0r0benzimidoyl)hexamethylenimine [1; Ar is 3-ClC I-1 n is 0, R is CH(CH N=Z is N(CH (from compound of Example B30 and hexamethylenimine), b.p. 114-119 C. (0045-0050 mm.), n =1.5418; hydrochloride salt, m.p. 175-178 C., colorless prisms from ethyl acetate.

Example C27: 1-[N-(n-Propyl)-3,4-dichlorobenzimidoyl] hexamethylenimine [1; Ar is 3,4-Cl C H n is 0, R is CH CH CH N=Z is N(CH (from compound of Example B31 and hexamethylenimine), hydrochloride salt, m.p. 18l-184 C. (dec.), colorless fiat needles from ethyl acetate.

Example C28: 1-(N-Is0pr0pyl-3,4-dichlorobenzimidoyl) hexametlzylenimine [1; Ar is 3,4CI C H n is 0, R is CH(CH N=Z is N(CH (from compound of Example B32 and hexamethylenimine), hydrochloride salt, m.p. 172-174 C., colorless needles from acetone.

Example C29: I-[N-(n-Propyl)-3-methoxy-4-chlor0benzimidoyl]hexamethylenimine [1; Ar is 3-CH O-4- CIC H n is 0, R is CH CH CH N=Z is N(CH (from compound of Example B33 and hexamethylenimine), hydrochloride salt, m.p. 164-165 C., colorless needles from ethyl acetate.

Example C30: 1-[N-(n-Propyl)-3,5-dichl0r0benzimid0yl] hexamethylenimine [1; Ar is 3,5-Cl C H n is 0, R is CH CH CH N=Z is N(CH (from compound of Example B34 and hexamethylenimine), hydrochloride salt, m.p. 115-116 C., colorless prisms from acetoneacetonitrile-ether.

Example C31: 1-(N-Isopropyl-2,4-aichlorobenzimia'oyl) hexamethylenimine [1; Ar is 2,4-Cl C H n is 0, R is CH(CH N=Z is N(CH (from compound of Example B35 and hexamethylenimine), hydrochloride salt, m.p. 220-223 C., colorless crystals from acetoneacetonitrile.

Example C32: J-[N-(n-Propyl)-2,4-dichl0r0benzimid0yl] hexamethylenimz'ne [1; Ar is 2,4-Cl C H n is 0, R is CH CH CH N=Z is N(CH (from compound of Example B36 and hexamethylenimine), hydrochloride salt, m.p. 126-120 C., colorless crystals from ethyl acetate.

Example C33: 1-(N-Isopropyl-4-triflaoromethoxybenzimid0yl)hexamethylenimine [1; Ar is 4-F COC H n is 0, R is CH(CH N=Z is N(CH (from compound of Example B37 and hexamethylenimine), p-toluenesulfonate salt, m.p. 154-156" C., colorless massive prisms from acetone-ether.

Example C34: 1-(N-Isopropyl-3,5-dichlorobenzimidoyl) hexamethylenimine [1; Ar is 3,5-Cl C H n is 0, R is CH(CH N=Z is N(CH (from compound of Example B38 and hexamethylenimine), hydrochloride 14 salt, m.p. 205-207 C., colorless prismatic blades from acetone-ether.

Example C35 (a) I-[N-(2-Chlor0ethyl) 4 chlorobenzimidoyl]hexamethylenimine [1; Ar is 4-ClC H n is 0, R is CH CH CI, N=Z is N(CH (from compound of Example B4 and hexamethylenimine), m.p. 68-70 C. (from n-pentane).

(b) 1-[N-(2-acetoxyethyl)-- 4 chlorobenzimidoyl]hexamezhylenimine [1; Ar is 4-ClC H n is 0, R is CH CH OCOCH N=Z is N(CH A mixture of 54.69 g. of 1-[N-(2-chloroethyl)-4-chlorobenzimidoyl]hexamethylenimine, 24.6 g. of potassium acetate and 200 ml. of dimethylformamide Was stirred at reflux for about sixteen hours. The reaction mixture was filtered and the filtrate evaporated to remove the solvent. The residue was partitioned between water and ether, and the ether layer was washed with Water, dried and concentrated. The residue was treated with 24.2 g. of cyclohexanesulfamic acid in acetone and the product precipitated with ether and n-pentane to give 1-[N-(2-acetoxyethyl) 4 chlorobenzimidoyl]hexamethylenimine in the form of its cyclohexanesulfamate salt, m.p. -112 C., colorless needles from isopropyl acetate.

Example C36 1 [N-(n Propyl) 2 nitro 4 ehlorobenzimidoyl] hexametltylenimine[1; Ar is 2-O' N-4-ClC H n is '0, R is CH CH CH N=Z is N(CH A solution of 27.88 g. of 1 [N (n propyl) 4- chlorobenzimidoyl]hexamethylenimine in ml. of concentrated sulfuric acid was cooled and 11 g. of potassium nitrate was added. The mixture was allowed to warm to room temperature and additional sulfuric acid was added until all solid dissolved. The reaction mixture was poured into one liter of ice and an excess of 35% sodium hydroxide. The product was extracted with ether and the ether extracts were dried and concentrated. The residue Was treated with hydrogen chloride gas to give l-[N-(npropyl) 2 nitro 4 chlorobenzimidoyl]hexamethylenimine in the form of its hydrochloride salt, m.p. 181- 183 C. and 194-196 C. (polymorphism), pale yellow platelets from ethyl acetate and acetone.

Example C37 1 (N isopropyl 4 chlorophenylacetimidoyl)hebtametlzyleniminefl; Ar is 4-ClC H n is l, R is CH(CH3)2, lS N(CH2)6].

A mixture of 20.1 g. of 1-(p-chlorophenylthioacetyl) hexamethylenimine (Example A43), 20.35 g. of mercuric chloride, 250 ml. of isopropylarnine and 500 ml. of methanol was stirred at room temperature for about sixteen hours. The reaction mixture was treated With activated charcoal, filtered, and the filtrate concentrated to remove the solvent. The residue was treated with dilute sodium hydroxide and extracted with ether. The ether extracts were dried and concentrated to give l-(N-isopropyl- 4 chlorophenylacetimidoyl)hexamethylenimine, obtained also in the form of its cyclohexanesulfamate salt, m.p. 150-152 C., colorless needles from acetonitrileacetone.

Example C38 1 [N (n Propyl) 4 chlarophenylacetimidoyl] hexamethylenimine [1; A ris 4-ClC H n is 1, R is CH CH CH N=Z is N(CH was prepared from 1 (p chlorophenylthioacetyl)hexamethylenimine (Example A43) and n-propylamine according to the procedure of Example C37, and was obtained in the form of its hydrochloride salt, m.p. -192 0., colorless needles from acetonitrile.

1 Example C39 1 [N (n Propyl) 4 aminobenzimidoyl]hexamethyleniminefl; Ar is 4-H NC H n is 0, R is CH2CH2CH3, is N 6] was prepared by hydrogenation of 1 [N (n propyl) 4 nitrobenzimidoyl]hexamethylenimine (Example C23) in 300 ml. of methanol in the presence of 0.5 g. of platinum oxide catalyst. Reduction was complete in ten minutes. The mixture was filtered and hydrogen chloride gas was passed through the filtrate. The solution was concentrated to remove the solvent, and the residue was recrystallized from ethanol to give 1 [N (n propyl) 4 aminobenzimidoyllhexamethylenimine in the form of its dihydrochloride salt, yellow prisms, m.p. 218-220 C.

Example C40 (a) 1 [N (3 Chloropropyl) 4 chlorobenzimidoyl] hexamethylenimine[1; Ar is 4-ClC H n is O, R is CH CH CH Cl, N=Z is N(CH (from compound of Example B39 and hexamethylenimine), yellow oil.

(b) 1 [N (3 Acetoxypropyl)-4-chl0r0benzimid0yl] hexamethylenimine [1; Ar is 4-ClC H n is 0, R is CH CHgCHgOCOCHg, is Was prepared from 1 [N (3 chloropropyl) 4 chlorobenzimidoyl]hexamethylenimine and potassium acetate in dimethylforrnamide according to the procedure of Example C(b). There was thus obtained 1-[N-(3- acetoxypropyl) 4 chlorobenzimidoyl]hexamethylenimine in the form of its ptoluenesulfonate salt, m.p. l44147 C., colorless prisms from ethyl acetate.

Example C41 1 [N (3 Hydraxypropyl) 4 chlorobenzimidoyl] hexamethylenimine [I; Ar is 4-ClC H n is 1, R is CH CH CH OH, N:Z is N(CH A mixture of 31.4 g. of 1 [N (3 acetoxypropyl)- 4 chlorobenzimidoyl]hexamethylenimine p toluenesulfonate, 150 ml. of methanol and a few crystals of p-toluenesulfonic acid monohydrate was refluxed for one week. The reaction mixture was concentrated to remove the solvent, and the residue was triturated with ether and recrystallized from ether-acetone to give 1 [N (3 hydroxypropyl) 4 chlorobenzimidoyl]hexamethylenimine in the form of colorless massive prisms, m.p. 129-130 C.

Example C42 1 (N Isopropyl 2,5 dichlorobenzimidoyl)hexamethyleniminefl; Ar is 2,5-Cl C H n is O, R is CH(CH N=Z is N(CH (from compound of Example B and hexamethylenimine), hydrochloride salt, m.p. 184-186 C., colorless prisms from acetone-ether.

Example C43 1 (N Isopropyl 3 nitro 4 chlorobenzimidoyl) hexamethyleniminefl; Ar is 3-O N-4-ClC H n is 0, R is *CH(CH N=Z is N(CH (from compound of Example B41 and hexamethylenimine), p-toluenesulfonate salt, m.p. 205-20 8 C., yellow prisms from acetone-ether.

Example C44 1 [N (n Propyl) 3 nitrobenzimidoyl]hexamethylenimine[I; Ar is 3-O NC H n is 0, R is CH CH CH N=Z is N(CH (from compound of Example B42 and hexamethylenimine), cyclohexanesulfamate salt, m.p. 134-136 C. (from acetone-ether).

Example C45 1 [N (n Propyl) 3 chlorobenzimidoyl]hexamethylenimine [1; Ar is 3'-'ClC H n is O, R is CH CH CH N:Z is N(CH was prepared by reacting N (npropyl) 3 chlorobenzamide with phosphorus pentachloridfi; and reacting the resulting N (n -propyl)- 3 chlorobenzimidyl chloride with hexamethylenimine. There was obtained 1 [N (n propyl) 3 chlorobenzimidoyl]hexamethylenimine in the form of its cyclohexanesulfamate salt, m.p. l49150 C., massive colorless prisms from acetone-methanol.

Example C46 1 [N (n Propyl) 3 amino 4 chlarobenzimz'doyl] hexamethylenimine[l; Ar is 3-NH -4-ClC H n is 0, R is CH CH CH N=Z is N(CH was prepared by reacting N (n propyl) 3 nitro 4 chlorobenzamide with phosphorus pentachloride, reacting the resulting N (n propyl) 3 nitro 4 chlorobenzimidyl chloride with hexamethylenimine, and catalytically hydrogenating the l-[N (n propyl)-3-nitro- 4 chlorobenzimidoyl]hexamethylenimine thus obtained. There was obtained 1 [N (npropyl) 3- amino 4 chlorobenzimidoyl]hexamethylenimine in the form of its cyclohexanesulfamate salt, yellow crystals, m.p. 149-153 C.

Example C47 1 [N (n-Propyl) 3 acetylamino 4 chlorobenzimidoyl]hexamethyleniminefl; Ar is 3-CH CONH-4- ClC H n is 0, R is CH CH CH N=Z is N(CH A mixture of 8.75 g. of 1 [N (n propyl) 3- amino 4 chlorobenzimidoyl]hexamethylenimine (Example C46) in the form of its cyclohexanesulfamate salt, 100 ml. of acetic anhydride and 3 drops of concentrated sulfuric acid was stirred at room temperature for about sixteen hours. The mixture was flash evaporated and the residue triturated with ether. The crystalline product was collected and recrystallized from acetonitrile-methanol to give 1.75 g. of 1 [N (n propyl) 3 acetylamino 4- chlorobenzimidoyl]hexamethylenimine, m.p. l-177 C.

Example C48 1 [N-(n Propyl)-4-chlor0-3-bis(methylsulfonyl)aminobenzimidoyl]hexamethylenmine [1; Ar is 3-(CH SO N-4'CIC6H3, n iS 0, R iS CH CH CH is N(CH2)6]- A mixture of 24.4 g. of 1-[N-(n-propyl)-3-amino-4- chlorobenzimidoyl]hexamethylenimine (Example C46), 16.96 g. of methanesulfonyl chloride and 250 ml. of dry pyridine was stirred at room temperature for about sixteen hours. The mixture Was flash evaporated and the crystalline product isolated and recrystallized from methanol-ether to give 9.88 g. of l-[N-(n-propyl)4-chloro-3- bis (methylsulfonyl) aminobenzimidoyl] hexamethylenimine, colorless prisms, m.p. 196-198 C.

Example C49 (a) 4-Chl0r0-3 tertiary-butylsalfamylbenzoic acid, m.p.

212-213 C., was prepared from 3-chlorosulfonyl-4- chlorobenzoic acid and tertiary-butylamine in chloroform solution.

(b) 4-Clzl0r0 3 tertiary-butylsulfamylbenzoyl chloride was prepared from 4-chloro-3-tertiary-butylsulfamoylbenzoic acid and thionyl chloride in dimethylformamide solution.

(0) 4 Chl0r0-3-tertiary-butylsulfamyl-N-(n-propyl)benzamide was prepared from 4-chloro3-tertiary-butylsulfamoylbenzoyl chloride and n-propylamine in chloroform, and had the m.p. 146-147 C. when recrystallized from isopropyl acetate.

(d) N-(n-Propyl)-4-chl0ro 3 tertiary butylsalfamylbenzz'midyl chloride was prepared from the benzamide of part (c) and phosphorus pentachloride.

(e) I-[N-(n Propyl) 4 chloro 3 tertiary-butylsulfamylbenzimidoyl]hexamethylenimine [1; Ar is 3- (CH3)3CNHSO2'4-C1C6H3, n is 0, R iS CH2CH2CH3, N=Z is N(CH was prepared from the benzimidyl chloride of part (d) and hexamethylenimine, and was obtained in the form of its cyclohexanesulfamate salt, colorless prisms, m.p. 8797 C.

1 7 Example C50 I-[N-(n-Propyl) 4 chloro 3 sulfamylbenzimidoyl] hexamethylenimine [1; Ar is 3H NSO -4-ClC H n is O, R is CH CH CH N=Z is N(CH was obtained in the form of its hydrochloride salt, m.p. 266-269 C., massive colorless prisms from 95% ethanol by treating 1 [N-(n-propyl)-4-chloro 3 tertiary-butylsulfamylbenzimidoyl]hexamethylenimine with concentrated hydrochloric acid, stirred at room temperature for about sixteen hours.

Example C51 (a) N-(mPropyl) 4 chloro 3 dimethylsulfamylbenzamide, m.p. 8991 C., was prepared from 4-chl0ro- 3-dirnethylsulfamylbenzoyl chloride and n-propylamine.

(b) N-(n Propyl) 4 chlr0-3-dimethylsulfamylbenzimidyl chloride was prepared from N (n-propyl)-4- chloro-3 dimet-hylsulfamylbenzamide and phosphorus pentachloride.

(c) I-[N-(n-Propyl) 4 chl0r0-3-dimethysulfamylbenzimidoyl]hexamethylenim ine [1; AI is 3-(CH NSO -4- ClC H n is 0, R is CH CH CH N=Z is N(CH was prepared from the benzimidyl chloride of part (b) and hexamethylenimine, and was obtained in the form of its cyclohexanesulfamate salt, massive colorless prisms, m.p. 162-164 C. when recrystallized from acetone-isopropyl alcohol-ether solution.

I claim: 1. A compound of the formula wherein Ar is unsubstituted pyridyl or phenyl substituted by from one to three substituents selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, nitro, lower-alkoxy, lower-alkylthio, lower-alkylsulfoxy, lower-alkylsulfonyl, amino, lower alkanoylamino, bis (methylsulfonyDamino, sulfarnyl, lower alkylsulfamyl, and di-lower-alkylsulfamyl; n is 0; N=Z is unsubstituted polymethylenimino having from 7 to 9 ring members; and R is lower-alkyl, lower-alkenyl, cycloalkyl of 3-6 ring members, cycloalkyl-lower-alkyl wherein cycloalkyl has 36 ring members, phenyl-lower alkyl, hydroxy-loweralkyl, or lower-alkanoyloXy-lower-alkyl.

2. A compound according to Claim 1 wherein n is 0, N:Z is hexamethylenimino, and R is lower-alkyl.

3. 1-(N-Lower-a1kenyl-p-halobenzirnidoyl)hexamethylenimine, according to Claim 1 wherein Ar is p-halophenyl, n is O, N=Z is hexamethylenimino and R is lower-alkenyl.

4. 1 (N-Cyclopropylmethyl-p-halobenzimidoyl)hexamethylenimine, according to Claim 1 wherein Ar is p-halophenyl, n is 0, N=Z is hexamethylem'mino and R is cyclopropylmethyl.

5. 1 (N-Lower-alkyl-p-halobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is p-halophenyl.

6. 1 (N-Phenyl-lower-alkyl-p-chlorobenzimidoyl)hexamethylenimine, according to Claim 1 wherein Ar is pchloroprenyl, n is 0, N=Z is hexamethylenimino and R is phenyl-lower-alkyl.

7. 1 (N-Lower-alkyl-2-nitro-4-chlorobenzimidyl)hexamethylenimine, according to Claim 1 wherein Ar is Z-nitro-4-chlorophenyl, n is 0, N=Z is hexamethylenimino and R is lower-alkyl.

8. 1 (N-Lower-alkyl-4 methoxybenzimidoyDhexamethylenimine, according to Claim 2 wherein Ar is pmethoxyphenyl.

9. 1 (N-Lower-alkyl 2 chlorobenzimidoyDhexamethylenimine, according to Claim 2 wherein Ar is o-chlorophenyl.

10. 1 (N Lower-alkylnicotinimidoyl)hexamethylenimine, according to Claim 1 wherein Ar is 3-pyridyl, n. is 0, N=Z is hexamethylenimino and R is lower-alkyl.

11. 1 (N Lower-alkyl-4 nitrobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is pnitrophenyl.

12. 1-(N Lower alkyl-3-ch1orobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is mchlorophenyl.

13. 1 (N Lower-alkyl-3,4-dichlorobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is 3,4- dichlorophenyl.

14. 1 (N lower-alkyl-3-methoxy-4-chlorobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is 3-methoXy-4-chlorophenyl.

15. 1 (N-Lower-alky1-3,S-dichlorobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is 3,5- dichlorophenyl.

16. 1 (N-Lower-alkyl-Z,4-dichlorobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is 2,4- dichlorophenyl.

17. 1 (N-Lower-alkyl-4-trifluoromethoxybenzimidoyl) hexamethylenimine, according to Claim 2 wherein Ar is p-trifluoromethoxyphenyl.

18. 1 (N Lower-alkyl 4 aminobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is paminophenyl.

19. 1 (N-Hydroxy-lower-alkyl-4-ohlorobenzimidoyl) hexamethylenimine, or the acetate thereof, according to Claim 1, wherein Ar is p-chlorophenyl, n is 0, N=Z is hexamethylenimino, and R is hydroxy-lower-alkyl or acetoxy-lower-al'kyl.

20. 1 (N-Lower-alkyl-2,S-dichlorobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is 2,5- dichlorophenyl.

21. 1 (N Lower-alkyl-3-lower-alkanoylamino-4chlorobenzimidoyl)hexamethylenimine, according to Claim 2 wherein Ar is 3-lower-alkanoylamino-4-chlorophenyl.

22. 1-[N-(n-Propyl)-3-amino 4 chlorobenzimidoyl] hexamethylenimine, according to Claim 1.

23. 1 (N Allyl-p-chlorobenzimidoyl)hexamethylenimine, according to Claim 3.

24. 1 [N-(n-Propyl) p chlorobenzimidoyHhexamethylenimine, according to Claim 5.

25. 1 (N-Benzyl p chlorobenzimidoyl)hexamethylenimine, according to Claim 6.

26. 1 [N-(Z-Phenylethyl)-p-chlorobenzimidoyl]hexamethylenimine, according to Claim 6.

27. 1 (N Allyl-4-bromobenzimidoyl)hexamethylenimine, according to Claim 3.

28. 1 (N-Cyclopropylmethyl p chlorobenzimidoyl) hexamethylenimine, according to Claim 4.

29. 1 (N Isopropyl-4-chlorophenylacetimidoyl)hexamethylenimine.

30. 1 (N Allyl-p-fiuorobenzimidoyl)hexamethylenimine, according to Claim 3.

31. 1 (N-Allyl-p trifiuoromethylbenzimidoyl)hexamethylenimine, according to Claim 1.

32. 1 (N-Cyclohexylmethyl-p-chlorobenzimidoyl)hexamethylenimine, according to Claim 1.

33. 1 [N (Z-Butenyl)-p-chlorobenzimidoyl]hexamethylenimine, according to Claim 3.

34. 1 [N-(n-Butyl)-p-chlorobenzimidoyl]hexamethylenimine, according to Claim 5.

35. 1 [N-(Z-Methylbutyl)-4-chlorobenzimidoyl]hexamethylenimine, according to Claim 5.

36. 1 [N-(n-Propyl)-4-iodobenzimidoyl]hexamethylenimine, according to Claim 5.

37. 1 (N Methyl-4-chlorobenzimidoyl)hexamethylenimine, according to Claim 5.

38. 1 [N-(n-Propyl)-2m'tro 4 chlorobenzimidoyl] hexamethylenimine, according to Claim 7.

39. 1 [N-(n Propyl)-4-methoxybenzimidoyl]hexamethylenimine, according to Claim 8.

40. 1 (N-Isopropyl-2-chlorobenzimidoyl)hexamethylenimine, according to Claim 9.

41. 1 (N Isopropyl 3-chlorobenzimidoyl)hexamethylenimine, according to Claim 12.-

42. 1 [N (n-Propyl)-3,4-dichlorobenzimidoyl]hexamethylenimine, according to Claim 13.

1 9 20 43. 1 [N- (n-Propyl)-4-nitrobenzimidoyl]hexamethyl- FOREIGN PATENTS enimine, according to Claim 11.

. 15,84 B 1 0 3 44. 1 [N-(n-PropyD-B-methoxy 4 chlorobenzunl- 7 9 11/1968 6 26 2 9 doyl]hexamethylenimine, according to Claim 14. HARRY 1' MOATZ Primary Examiner References Cited 5 U S CL X R UNITED STATES PATENTS 424-244; 260566 D, 239 BF, 499 CD, 556 A, 556 AR, 2,211,280 8/1940 Martin et a1 260-564 R 562 R 3,598,800 8/1971 Gitzi 260564 R 3,125,573 3/1964 Elpern 260564 10 

1. A COMPOUNDD OF THE FORMULA 